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Memory Trace in Mouse Hippocampus

Credit:Sahay Lab, Massachusetts General Hospital, Boston

Play the first few bars of any widely known piece of music, be it The Star-Spangled Banner, Beethoven’s Fifth, or The Rolling Stones’ (I Can’t Get No) Satisfaction, and you’ll find that many folks can’t resist filling in the rest of the melody. That’s because the human brain thrives on completing familiar patterns. But, as we grow older, our pattern completion skills often become more error prone.

This image shows some of the neural wiring that controls pattern completion in the mammalian brain. Specifically, you’re looking at a cross-section of a mouse hippocampus that’s packed with dentate granule neurons and their signal-transmitting arms, called axons, (light green). Note how the axons’ short, finger-like projections, called filopodia (bright green), are interacting with a neuron (red) to form a “memory trace” network. Functioning much like an online search engine, memory traces use bits of incoming information, like the first few notes of a song, to locate and pull up more detailed information, like the complete song, from the brain’s repository of memories in the cerebral cortex.


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Mammalian hippocampal tissue

Caption: Mammalian hippocampal tissue. Immunofluorescence microscopy showing neurons (blue) interacting with neural astrocytes (red) and oligodendrocytes (green).
Credit: Jonathan Cohen, Fields Lab, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH

There’s been considerable debate about whether the human brain has the capacity to make new neurons into adulthood. Now, a recently published study offers some compelling new evidence that’s the case. In fact, the latest findings suggest that a healthy person in his or her seventies may have about as many young neurons in a portion of the brain essential for learning and memory as a teenager does.

As reported in the journal Cell Stem Cell, researchers examined the brains of healthy people, aged 14 to 79, and found similar numbers of young neurons throughout adulthood [1]. Those young neurons persisted in older brains that showed other signs of decline, including a reduced ability to produce new blood vessels and form new neural connections. The researchers also found a smaller reserve of quiescent, or inactive, neural stem cells in a brain area known to support cognitive-emotional resilience, the ability to cope with and bounce back from stressful circumstances.

While more study is clearly needed, the findings suggest healthy elderly people may have more cognitive reserve than is commonly believed. However, the findings may also help to explain why even perfectly healthy older people often find it difficult to face new challenges, such as travel or even shopping at a different grocery store, that wouldn’t have fazed them earlier in life.


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Steve Ramirez

Steve Ramirez/Joshua Sariñana

Whether it’s lacing up for a morning run, eating blueberry scones, or cheering on the New England Patriots, Steve Ramirez loves life and just about everything in it. As an undergraduate at Boston University, this joie de vivre actually made Ramirez anxious about choosing just one major. A serendipitous conversation helped him realize that all of the amazing man-made stuff in our world has a common source: the human brain.

So, Ramirez decided to pursue neuroscience and began exploring the nature of memory. Employing optogenetics (using light to control brain cells) in mice, he tagged specific neurons that housed fear-inducing memories, making the neurons light sensitive and amenable to being switched on at will.

In groundbreaking studies that earned him a spot in Forbes 2015 “30 Under 30” list, Ramirez showed that it’s possible to reactivate memories experimentally in a new context, recasting them in either a more negative or positive behavior-changing light [1–3]. Now, with support from a 2016 NIH Director’s Early Independence Award, Ramirez, who runs his own lab at Boston University, will explore whether activating good memories holds promise for alleviating chronic stress and psychiatric disease.


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Elixir of youth?For centuries, people have yearned for an elixir capable of restoring youth to their aging bodies and minds. It sounds like pure fantasy, but, in recent years, researchers have shown that the blood of young mice can exert a regenerative effect when transfused into older animals. Now, one of the NIH-funded teams that brought us those exciting findings has taken an early step toward extending them to humans.

In their latest work published in Nature, the researchers showed that blood plasma collected from the umbilical cords of newborn infants possesses some impressive rejuvenating effects [1]. When the human plasma was infused into the bloodstream of old mice, it produced marked improvements in learning and memory. Additional experiments traced many of those cognitive benefits to a specific protein called TIMP2—an unexpected discovery that could pave the way for the development of brain-boosting drugs to slow the effects of aging.


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Caption: Colorized 3D reconstruction of dendrites. Neurons receive input from other neurons through synapses, most of which are located along the dendrites on tiny projections called spines.
Credit: The Center for Sleep and Consciousness, University of Wisconsin-Madison School of Medicine

People spend about a third of their lives asleep. When we get too little shut-eye, it takes a toll on attention, learning and memory, not to mention our physical health. Virtually all animals with complex brains seem to have this same need for sleep. But exactly what is it about sleep that’s so essential?

Two NIH-funded studies in mice now offer a possible answer. The two research teams used entirely different approaches to reach the same conclusion: the brain’s neural connections grow stronger during waking hours, but scale back during snooze time. This sleep-related phenomenon apparently keeps neural circuits from overloading, ensuring that mice (and, quite likely humans) awaken with brains that are refreshed and ready to tackle new challenges.


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